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Golub A.G.,NASU Institute of Molecular Biology and Genetics | Bdzhola V.G.,NASU Institute of Molecular Biology and Genetics | Briukhovetska N.V.,NASU Institute of Molecular Biology and Genetics | Balanda A.O.,NASU Institute of Molecular Biology and Genetics | And 5 more authors.
European Journal of Medicinal Chemistry | Year: 2011

A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC 50 values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2. © 2010 Elsevier Masson SAS. All rights reserved. Source


Starosyla S.A.,NASU Institute of Molecular Biology and Genetics | Volynets G.P.,NASU Institute of Molecular Biology and Genetics | Bdzhola V.G.,NASU Institute of Molecular Biology and Genetics | Golub A.G.,Otava Ltd. | And 2 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2014

The three-dimensional pharmacophore model of apoptosis signal-regulating kinase 1 (ASK1) inhibitors has been developed with PharmaGist program. The positions of pharmacophore features in the model correspond to conformations of ASK1 highly active inhibitors in which they interact with ATP-binding site of ASK1. The generated pharmacophore model allows accurately predict active and inactive compounds and can be of great use for virtual screening aimed at discovering novel ASK1 inhibitors. © 2014 Elsevier Ltd. All rights reserved. Source


Golub A.G.,NASU Institute of Molecular Biology and Genetics | Bdzhola V.G.,NASU Institute of Molecular Biology and Genetics | Kyshenia Y.V.,NASU Institute of Molecular Biology and Genetics | Sapelkin V.M.,NASU Institute of Molecular Biology and Genetics | And 5 more authors.
Molecular and Cellular Biochemistry | Year: 2011

Serine/threonine protein kinase CK2 controls vast variety of fundamental processes in cell life; however, despite long period of study, its functional role is not completely determined. CK2 has a significant pathogenic potential and its activity is strictly associated with the development of various kinds of disorders. There are a growing number of facts that inhibitors of CK2 could be used as pharmaceutical agents for the cancer treatment, viral infections, and inflammatory diseases. In this article, we report structural and biological data on the novel synthetic flavonol derivatives, 3-hydroxy-4′- carboxyflavones, possessing a high inhibitory activity toward CK2. With the aid of combinatorial organic synthesis, molecular modeling techniques and biochemical in vitro tests, we studied the structure-activity relationships of flavonol derivatives and developed binding model describing their key intermolecular interactions with the CK2 ATP-binding site. Obtained data show that the synthetic 3-hydroxy-4′-carboxyflavones possess the highest activity among flavonol inhibitors of CK2 known till date. © Springer Science+Business Media, LLC. 2011. Source


Starosyla S.A.,NASU Institute of Molecular Biology and Genetics | Volynets G.P.,NASU Institute of Molecular Biology and Genetics | Lukashov S.S.,NASU Institute of Molecular Biology and Genetics | Gorbatiuk O.B.,NASU Institute of Molecular Biology and Genetics | And 3 more authors.
Bioorganic and Medicinal Chemistry | Year: 2015

Apoptosis signal-regulating kinase 1 (ASK1) plays important roles in the pathogenesis of type 1 and type 2 diabetes, autoimmune disorders, cancer and neurodegenerative diseases suggesting that small compounds inhibiting ASK1 could be used for the treatment of these pathologies. We have identified novel chemical class of ASK1 inhibitors, namely benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one, using molecular modeling techniques. It was found that the most active compound 1-(6-fluoro-benzothiazol-2-yl)-3-hydroxy-5-[3-(3-methyl-butoxy)-phenyl]-4-(2-methyl-2,3-dihydro-benzofuran-5-carbonyl)-1,5-dihydro-pyrrol-2-one (BPyO-34) inhibits ASK1 with IC50 of 0.52 μM in vitro in kinase assay. The structure-activity relationships of 34 derivatives of benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one have been studied and binding mode of this chemical class has been proposed. © 2015 Elsevier Ltd. All rights reserved. Source


Golub A.G.,Otava Ltd. | Bdzhola V.G.,NASU Institute of Molecular Biology and Genetics | Ostrynska O.V.,NASU Institute of Molecular Biology and Genetics | Kyshenia I.V.,NASU Institute of Molecular Biology and Genetics | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2013

Human protein kinase CK2 is one of the most intriguing enzymes, which functional role still remains unclear despite of decades of studying. At present there is abundant evidence pointing to the fact that inhibitors of CK2 could be used as pharmaceutical agents to treat cancer, viral infections and inflammatory diseases. Here we report novel synthetic flavone inhibitors, 4′-hydroxyflavones, possessing high activity towards CK2. These compounds were identified with receptor-based virtual screening and then chemically optimized on the base of rationale derived from biochemical screening and molecular modeling. It has been demonstrated that synthetic flavone derivatives are much more potent CK2 inhibitors than the natural ones, and we believe that their further examination will be helpful for studying biological role of CK2 as well as for development of new kinase-oriented drugs. © 2013 Elsevier Ltd. All rights reserved. Source

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